FDA Approves Denosumab for the Treatment of Hypercalcemia of Malignancy Refractory to Bisphosphonate Therapy


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The U.S. Food and Drug Administration has approved a new indication for denosumab (Xgeva) for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Denosumab was approved and granted Orphan Drug designation by the FDA, which is reserved for drugs that are intended for the treatment of rare diseases affecting fewer than 200,000 people in the United States.

Hypercalcemia of malignancy is a serious complication in patients with advanced cancer, including those with hematologic malignancies, and indicates a poor prognosis. The condition results from cancer-driven increases in bone resorption and, if untreated, can lead to renal failure, progressive mental impairment, coma, and death. In 2012, the estimated prevalence of hypercalcemia in cancer patients in the United States was 2.7%.

Clinical Study

The approval is based on positive results from an open-label, single-arm study, which enrolled patients with advanced cancer and persistent hypercalcemia after recent bisphosphonate treatment. The primary endpoint was the proportion of patients with a response, defined as albumin-corrected serum calcium (CSC) < 11.5 mg/dL within 10 days after the first dose of denosumab. Secondary endpoints included the proportion of patients who experienced a complete response (defined as CSC < 10.8 mg/dL) by day 10, time to response, and response duration (defined as the number of days from the first occurrence of CSC < 11.5 mg/dL).

The study achieved its primary endpoint, with a response rate at day 10 of 63.6% in the 33 patients evaluated. The overall complete response rate was 63.6%. The estimated median time to response (CSC < 11.5 mg/dL) was 9 days, and the median duration of response was 104 days.

The most common adverse reactions in patients receiving denosumab for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea. ■



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